镉诱导大鼠腺垂体细胞凋亡及与p38 MAPK&ERK1/2途径介导机制关系的初步研究  

Effect on apoptosis of anterior pituitary induced by cadmium chloride and its relations with p38 MAPK&ERK1/2 passway

作　　者：杨杏芬[1] 朱伟[2] 魏青[3] 林忠宁[3] 郑树声[4] 赵敏[3] 陈铁江[3] 范瑞全[3] 

机构地区：[1]广东省疾病预防控制中心,广州510300 [2]广州市疾病预防控制中心毒理科 [3]中山大学公共卫生学院 [4]中山大学分子医学中心图像分析室

出　　处：《卫生研究》2005年第6期681-684,共4页Journal of Hygiene Research

基　　金：广东省自然科学基金资助项目(No.021990)

摘　　要：目的了解CdCl2对腺垂体的损伤以及细胞凋亡发生与p38MAPK、ERK12表达的关系,为了解镉致腺垂体毒作用的分子机制提供科学依据。方法采用健康雄性SD大鼠进行整体试验(n=12),分别每天经口灌胃给予0、1.0、2.0、4.0mgkgbwCdCl2,6周后取腺垂体进行指标检测;离体试验采用酶解分离大鼠之原代腺垂体细胞,分别以0、1.56、3.12、6.25、12.50、25.00、50.00、100.00μmolLCdCl2处理,收获细胞进行检测;特异性阻断剂阻断凋亡效应的试验采用2.65μmolLp38MAPK的特异阻断剂SB203580或10μmolLERK12激酶的特异阻断剂U0126处理细胞,然后以3.12μmolL或100.00μmolL的CdCl2处理细胞后进行相应的检测。检测指标包括:TUNEL法和流式细胞术等检测凋亡。结果整体实验和离体实验结果均显示CdCl2以剂量依赖方式诱导腺垂体细胞发生凋亡(P<0.05);特异性阻断剂效应的研究结果显示2.65μmolLSB203580和10μmolLU0126对TUNEL阳性细胞的相对灰度和凋亡细胞率均有一定的影响。结论在一定的剂量条件下,CdCl2影响腺垂体激素分泌水平,并导致发腺垂体细胞凋亡,MAPKs家族成员p38MAPK和ERK12激酶通路在凋亡发生过程中可能发挥一定的作用。Objective To study the effects of cadmium chloride on anterior pituitary and the relation between p38 MAPK＆ERK1/2 passway and apoptosis induced by cadmium chloride. Methods In vivo studies, SD male rats were administered with CdCI： at the doses of 0, 1.0, 2.0, 4.0mg/kg bw by garage for 6 weeks. In vitro studies, rats＇ anterior pituitary cells were primarily cultured and then treated with CdCl2 at doses of 0,1.56,3.12,6.25,12.50,25.00,50.00, 100.00μmol/L for 6 hours. Inhabiting study, cells were incubated with SB203580 （2.65μmol/L） or U0126 （10μmol/L） respectively for 2 hours and then treated with CdCI： at doses of 3.12, 100.00μmol/L for 6 hours. The indices in above experiments included expression of TUNEL-positive cells, rate of apoptosis by Flowcytometry. Results The results showed that the apoptosis induced by CdCl2 inclined to enhance with dose dependent manner. Further more, U0126 and SB203580, the specific inhibitor of ERK1/2 and p38 MAPK respectively, could decrease the expression of TUNEL-positive cells significantly and lower apoptotic rate of primary cultured anterior pituitary cells. Conclusion It was suggested that cadmium induce apoptosis of anterior pituitary both in vivo and in vitro in dose-dependent manner, ERK1/2 and p38 MAPK passways might play a role during above processes.

关 键 词：镉 腺垂体 细胞凋亡 MAPKS ERK1/2激酶 p38 MAPK 

分 类 号：R114[医药卫生—卫生毒理学] Q255[医药卫生—公共卫生与预防医学]